Mrs. Landingham appears in the very first episode of The West Wing. She is the personal secretary to President Josiah Bartlet, and to a large extent controls access by the other characters to the President. She is the only White House staffer whom the President nearly always addresses formally; he typically calls her "Mrs. Landingham," although he addresses other, more senior members of his staff, and Mrs. Landingham's eventual replacement, by their first names. In the show, she describes herself as a surrogate big sister to Bartlet.

In the second season 21st episode "18th and Potomac", Mrs. Landingham is killed by a drunk driver while driving to the White House to show the President (at his request) a new car she just bought. Her death affects President Bartlet deeply, driving the plot of the second-season finale "Two Cathedrals", in which Bartlet must decide whether to seek re-election in the midst of a scandal over failing to publicly disclose the fact that he has multiple sclerosis. In flashbacks during this episode it is revealed that she first met Bartlet when he was a teenager in his native New Hampshire, where his father served as headmaster of a private school. Mrs. Landingham (played by Kirsten Nelson in the flashback episodes) was at that time Bartlet's father's secretary. In another flashback in the episode "Bartlet for America" Mrs. Landingham is shown working as Jed Bartlet's secretary during his tenure as Governor.

Landingham was married to Air Force Major Henry Landingham, who served in the Korean War, though she is a widow by the time she begins work at the White House. It is revealed in "In Excelsis Deo" that her twin sons (Andrew and Simon) were killed in the Vietnam War on Christmas Eve, 1970. The twins' lottery number had come up while in medical school and despite their parents' strong opposition, they decided not to get a deferment, wanting instead to "go where people needed doctors".